Advances in RNA vaccines for preventive indications: A case study of a vaccine against rabies
Open accessAbstract
There is a global need for effective and affordable rabies vaccines, which is unmet by current vaccines due to limitations in their production capacities, required administration schedules, storage requirements, and cost. Many different experimental approaches previously used for bacterial and viral vaccines have been applied to rabies, but with variable success. One of the most promising new concepts is the use of messenger RNA (mRNA) in encoding the main rabies virus antigen, the envelope glycoprotein (RABV-G). CureVac has applied their proprietary technology platform for the production of mRNA to this problem, resulting in the rabies vaccine candidate CV7201. Following preclinical studies in mice and pigs showing that CV7201 could induce neutralizing immune responses that protected against rabies virus, different dosages and routes of administration of CV7201 were tested in a phase 1 human study. This clinical study proved that mRNA vaccination was safe and had an acceptable reactogenicity profile, but immune responses depended on the mode of administration, and they did not unequivocally support CV7201 for further development as a prophylactic vaccine with this particular formulation. Further, preclinical studies using RABV-G mRNA encapsulated in lipid nanoparticles (LNPs) showed an improved response in both mice and nonhuman primates, and these encouraging results are currently being followed up in clinical studies in humans. This review summarizes the recent advances in mRNA vaccines against rabies.
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Preclinical studies showed that protecting the mRNA by lipid encapsulation significantly enhanced the response to CV7201.
“preclinical studies showed that protecting the mRNA by lipid encapsulation significantly enhanced the response to the CV7201 [9], [24].”
From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [24]
Section 3 reports that lipid-nanoparticle encapsulation substantially increased antibody responses to rabies-glycoprotein mRNA in mice compared with plain mRNA. But Section 2.1 identifies CV7201 as a protamine-formulated vaccine, while Section 3 identifies the LNP formulation as CV7202. The enhanced response is therefore supported for the LNP-formulated rabies mRNA, not for CV7201 as named in the claim. (LLM, conf=0.88)
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Cites
mRNA vaccines — a new era in vaccinology
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines
Hassett, K. J., Benenato, K. E., Jacquinet, E., Lee, A., Woods, A., Yuzhakov, O., Himansu, S., Deterling, J., Geilich, B. M., Ketova, T., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.01.013 · Cited by 927 · see citing works
Advances in mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 680 · see citing works
Nonviral delivery of self-amplifying RNA vaccines
Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209367109 · Cited by 675 · cited 1× · see citing works
“[40] was that replicating nonmodified mRNA molecules formulated as lipid nanoparticles (LNPs) were able to induce protective immune responses in mice against respiratory syncytial virus (RSV).”
BackgroundDeveloping mRNA-vaccine technologies
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622 · see citing works
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · see citing works
Self-citationAlberer, M., Gnad-Vogt, U., Hong, H. S., Mehr, K. T., Backert, L., Finak, G., Gottardo, R., Bica, M. A., Garofano, A., Koch, S. D., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31665-3 · Cited by 530 · see citing works
INNATE IMMUNE RESPONSE IN TH1- AND TH2-DOMINANT MOUSE STRAINS
Watanabe, H. A., Numata, K., Ito, T., Takagi, K., & Matsukawa, A. (2004) · Shock · doi:10.1097/01.shk.0000142249.08135.e9 · Cited by 522 · see citing works
mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases
Maruggi, G., Zhang, C., Li, J., Ulmer, J. B., & Yu, D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.01.020 · Cited by 507 · see citing works
Petsch, B., Schnee, M., Vogel, A. B., Lange, E., Hoffmann, B., Voss, D., Schlake, T., Thess, A., Kallen, K.-J., Stitz, L., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2436 · Cited by 461 · see citing works
Self-citationChemokines: key players in innate and adaptive immunity
Esche, C., Stellato, C., & Beck, L. A. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23841.x · Cited by 385 · see citing works
Fotin-Mleczek, M., Duchardt, K. M., Lorenz, C., Pfeiffer, R., Ojkić-Zrna, S., Probst, J., & Kallen, K.-J. (2011) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181f7dbe8 · Cited by 335 · cited 1× · see citing works
“We have been applying our expertise with mRNA to target different infectious diseases employing a range of additional technologies to augment and direct the immune response [26,27].”
MethodCorrection: Estimating the Global Burden of Endemic Canine Rabies
Hampson, K., Coudeville, L., Lembo, T., Sambo, M. B., Kieffer, A., Attlan, M., Barrat, J., Blanton, J. D., Briggs, D. J., Cleaveland, S., et al. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0003786 · Cited by 328 · see citing works
Antigenic Properties of Rabies Virus Components
Wiktor, T. J., György, E., Schlumberger, H. D., et al. (1973) · The Journal of Immunology · doi:10.4049/jimmunol.110.1.269 · Cited by 283 · see citing works
COMPASS identifies T-cell subsets correlated with clinical outcomes
Lin, L., Finak, G., Ushey, K., Seshadri, C., Hawn, T. R., Frahm, N., Scriba, T. J., Mahomed, H., Hanekom, W. A., Bart, P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3187 · Cited by 282 · see citing works
Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines
Lutz, J., Lazzaro, S., Habbeddine, M., Schmidt, K. E., Baumhof, P., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., Heidenreich, R., et al. (2017) · npj Vaccines · doi:10.1038/s41541-017-0032-6 · Cited by 257 · see citing works
WHO Expert Consultation on Rabies : first report
Rabies, W. E. C. O. (2005) · World Health Organization eBooks · Cited by 243 · see citing works
Schnee, M., Vogel, A. B., Voss, D., Petsch, B., Baumhof, P., Kramps, T., & Stitz, L. (2016) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0004746 · Cited by 212 · cited 11× · see citing works
“) rabies challenge infection in mice (adapted from reference [31]).”
BackgroundInfluentialSelf-citationTordo, N., Poch, O., Ermine, A., et al. (1988) · Virology · doi:10.1016/0042-6822(88)90600-9 · Cited by 203 · see citing works
Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication
Minor, P. D. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.02.071 · Cited by 183 · see citing works
The history of rabies in the Western Hemisphere
Velasco-Villa, A., Mauldin, M. R., Shī, M., et al. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.03.013 · Cited by 150 · see citing works
Difficulties in estimating the human burden of canine rabies
Taylor, L. H., Hampson, K., Fahrion, A. S., et al. (2015) · Acta Tropica · doi:10.1016/j.actatropica.2015.12.007 · Cited by 128 · see citing works
Developments in rabies vaccines
Hicks, D., Fooks, A. R., & Johnson, N. (2012) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2012.04592.x · Cited by 122 · see citing works
Protection of pigs against Aujeszky's disease by DNA vaccination.
Gerdts, V., Mettenleiter, T. C., Makoschey, B., et al. (1997) · Journal of General Virology · doi:10.1099/0022-1317-78-9-2139 · Cited by 117 · see citing works
Overview, Prevention, and Treatment of Rabies
Hankins, D. G., & Rosekrans, J. A. (2004) · Mayo Clinic Proceedings · doi:10.4065/79.5.671 · Cited by 103 · see citing works
Quiambao, B. P., Dimaano, E. M., Ambas, C., et al. (2004) · Vaccine · doi:10.1016/j.vaccine.2004.09.027 · Cited by 99 · see citing works
From brain passage to cell adaptation: the road of human rabies vaccine development
Wu, X., Smith, T. G., & Rupprecht, C. E. (2011) · Expert Review of Vaccines · doi:10.1586/erv.11.140 · Cited by 93 · see citing works
Barth, R., Gruschkau, H., Bijok, U., et al. (1984) · Journal of Biological Standardization · doi:10.1016/s0092-1157(84)80019-0 · Cited by 51 · see citing works
Rabies vaccine development by expression of recombinant viral glycoprotein
Astray, R. M., Jorge, S. A. C., & Pereira, C. A. (2016) · Archives of Virology · doi:10.1007/s00705-016-3128-9 · Cited by 44 · see citing works
Human rabies transmitted by dogs: current status of global data, 2015.
(2016) · PubMed · Cited by 43 · see citing works
New human rabies vaccines in the pipeline
Fooks, A. R., Banyard, A. C., & Ertl, H. C. J. (2018) · Vaccine · doi:10.1016/j.vaccine.2018.08.039 · Cited by 41 · see citing works
Diallo, M. K., Diallo, A. O., Dicko, A., et al. (2019) · BMC Infectious Diseases · doi:10.1186/s12879-019-3928-0 · Cited by 39 · see citing works
Comparison of DNA application methods to reduce BRSV shedding in cattle
Schrijver, R. S., Langedijk, J. P. M., Keil, G. M., et al. (1998) · Vaccine · doi:10.1016/s0264-410x(97)00198-9 · Cited by 35 · see citing works
Quiambao, B. P., Dy-Tioco, H. Z., Dizon, R. M., et al. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.09.036 · Cited by 33 · see citing works
Javier, R. S., Kunishita, T., Koike, F., et al. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90192-5 · Cited by 31 · see citing works
Animal Models in the Pathogenesis and Treatment of Rabies
Baer, G. Μ. (1988) · Clinical Infectious Diseases · doi:10.1093/clinids/10.supplement_4.s739 · Cited by 24 · see citing works
Mooij, P., Grødeland, G., Koopman, G., Andersen, T. K., Mortier, D., Nieuwenhuis, I. G., Verschoor, E. J., Fagrouch, Z. C., Bogers, W. M. J. M., & Bogen, B. (2019) · Vaccine · doi:10.1016/j.vaccine.2018.12.049 · Cited by 22 · see citing works
Ullas, P. T., Desai, A. S., & Madhusudana, S. N. (2014) · Clinical and Experimental Vaccine Research · doi:10.7774/cevr.2014.3.2.202 · Cited by 9 · see citing works
Flagged first, then by citations
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Sorted by citations
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
Nanomaterial Delivery Systems for mRNA Vaccines
Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582 · see citing works
mRNA vaccines manufacturing: challenges and bottlenecks
Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M., & Marques, M. P. C. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.03.038 · Cited by 545 · see citing works
Self-amplifying RNA vaccines for infectious diseases
Bloom, K., van den Berg, F., & Arbuthnot, P. (2021) · Gene Therapy · doi:10.1038/s41434-020-00204-y · Cited by 487 · see citing works
Aldrich, C., Leroux–Roels, I., Huang, K. B., Bica, M. A., Loeliger, E., Schoenborn-Kellenberger, O., Walz, L., Leroux-Roels, G., von Sonnenburg, F., & Oostvogels, L. (2021) · Vaccine · doi:10.1016/j.vaccine.2020.12.070 · Cited by 204 · see citing works
“CV7201 was generally well tolerated but the induction of adequate immune responses was dependent upon the mode of administration of the vaccine, notably requiring intradermal or intramuscular administration with specialized devices.”
BackgroundInfluentialSafety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques
Li, J., Yu, P., Liu, Q., Xu, L., Chen, Y., Li, Y., Zhang, F., Zhu, W., & Peng, Y. (2024) · npj Vaccines · doi:10.1038/s41541-024-00925-w · Cited by 24 · see citing works
- Authors
- Armbruster, N., Jasny, E., & Petsch, B.
- Affiliations
- CureVac (Germany) (DE)
- Corresponding author
- Petsch, Benjamin
- ORCID
- Petsch, Benjamin
- Venue
- Vaccines
- Publisher
- MDPI AG
- Published
- 2019-09-27
- Volume
- 7
- Issue
- 4
- Pages
- 132
- ISSN
- 2076-393X (ISSN-L)
- PMC
- PMC6963972
- OpenAlex
- W2976537775
- Cited by
- 95
- References
- 39
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 18 · 2023: 10 · 2022: 24 · 2021: 19 · 2020: 11
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Vaccines (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- rabies vaccine, mRNA vaccines, rabies virus glycoprotein, lipid nanoparticles, prophylactic vaccination, neutralizing antibodies, route of administration, non-human primates
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